Gliomas remain one of the deadliest forms of cancer. Improved therapeutics will require a better understanding of the molecular nature of these tumors (1). Chemokine receptors have recently been found to play a role in the tumorigenesis of glioma and many other cancers. Among these Chemokine receptors, CXCR4 is considered to be a major Chemokine receptor on glioma cells and mediates their survival (2). However, the mechanisms underlying the effect of Chemokine receptors in glioma remain largely unknown. We identified aurora related kinase 1 (ARK1) as a CXCR4 binding protein. AKR1 has been demonstrated to be involved in tumorigenesis. We hypothesize that ARK1 is involved in the CXCR4-initiated signaling pathways resulting in proliferation of glioma cells. In the proposed studies, the interaction of CXCR4 with ARK1 will be investigated and the role of the interactions in CXCR4 signal transduction and intracellular trafficking, as well as in glioma cell proliferation and migration will be evaluated. The proposed studies will provide significant insight into the mechanism underlying the role of CXCR4 in tumorgenesis and metastasis, and may lead to novel therapeutic approaches for the treatment of glioma.